- Email: [email protected]
Current overview of statin induced myopathy
Methods: HIV-infected patients hospitalized with ACS between 1993–2003 (n⫽68) had clinical features and outcomes compared with those of 68 randomly selected control patients with ACS without HIV. Results: Compared to controls, HIV patients were on average more than a decade younger, male, and current smokers with low HDL cholesterol levels. They were less likely than controls to have diabetes or hyperlipidemia, and had lower TIMI (Thrombolysis in Myocardial Infarction trial) risk scores on admission. At coronary angiography, the number of vessels with ⬎50% stenosis was 1.3⫾1.0 in HIV patients and 1.9⫾1.2 in controls (p⫽0.007). Restenosis occurred in significantly fewer HIV patients who underwent percutaneous coronary intervention (PCI) compared with controls (52% vs. 14%, p⫽0.006). Conclusions: HIV patients with ACS are younger, male, and are current smokers with low HDL cholesterol levels compared with other ACS patients. While their TIMI risk scores are lower, and they are more likely to have single-vessel disease, their restenosis rates after PCI are unexpectedly high. Perspective: This study highlights important clinical features of HIV patients presenting with ACS. Because of an increased incidence of ACS among HIV patients, they should be targeted for both primary and aggressive secondary prevention. RM
72.0 – 89.5%]) and cardiac rehabilitation referral (34% [95% CI, 25.9 –39.7%] to 73% [95% CI, 63.2– 82.9%]). An improving trend was also seen in blood pressure control (60% [95% CI, 55.3– 65.6%] to 68% [95% CI, 60.2–76.1%]). High baseline use was sustained for use of aspirin, beta-blockers, and ACE inhibitors. Conclusions: A collaborative quality improvement initiative using interactive training of hospital teams with physician champions, and the use of an interactive Web-based patient management tool improved adherence to prevention guidelines in hospitalized patients with CAD. Perspective: The Guideline Applied in Practice (GAP) and the Get With The Guidelines (GWTG) quality improvement initiatives demonstrate that implementation of system changes is successful in improving the quality of care of patients with CAD that ultimately results in improved outcomes of these patients. RM
Current Overview of Statin Induced Myopathy Rosenson RS. Am J Med 2004;116:408 –16. Purpose: To summarize the current knowledge and clinical implications regarding statin-induced myopathy and review the ACC/AHA/NHLBI task force recommendations. Definitions and Prevalence: Myalgia, defined as muscle ache or weakness without increase in creatine kinase levels (CK), is the most frequently occurring adverse reaction to statin therapy. It is reversible on drug withdrawl, and symptoms resolve in 2–3 weeks. Myositis is defined as muscle symptoms with increased CK levels. Rhabdomyolysis (rhabdo) is defined as muscle symptoms associated with CK levels ⬎10 times upper limit of normal, and can be life threatening. Dose-dependent myotoxic effects from myalgia to rhabdo ranges from 1–7%. Myopathy, a disease of muscle that can occur in the absence of CK elevation, is rare, with an incidence of 1.2/10,000 person-years, which is similar to the general population. Rhabdomyolysis occurred in 0.05% of patients receiving simvastatin and 0.03% on placebo in the Heart Protection Study. Cerivastatin (most on 0.8 mg dose) caused 31 fatal cases of rhabdo in the U.S., and 12 were on concomitant gemfibrozil. Cerivastatin had a 16- to 80-fold higher rate of rhabdo than did other statins (3.16/ million with ceriva, 0.19 lova, 0.12 simva, 0.04 atorva, 0.04 prava and 0 with fluva). Lipophilicity is believed to increase the possibility of adverse effects on muscle, but prava and rosuva, which are both hydrophilic, do not seem to have fewer muscle issues. The risk of myopathy increases with age, in women, in renal failure, with concomitant use of drugs that inhibit or use the CYP3A4 pathway (e.g., cyclosporine, erythromycin, anti-fungals), grapefruit juice, and hypothyroidism. Concomitant use of gemfibrozil inhibits glucuronidation, a common metabolic pathway for hydroxyl acid forms of statins, and marked increases statin concentration and risk of myopathies. In contrast, fenofibrate does not have the same effects and may be safer with the statins. The combination of statin ⫹ fibrate would be
Get With the Guidelines for Cardiovascular Secondary Prevention. Pilot Results LaBresh KA, Ellrodt AG, Gliklich R, Liljestrand J, Peto R. Arch Intern Med 2004;164:203–9. Study Question: Does the use of Web-based technology and a collaborative model improve hospital adherence to secondary prevention guidelines? Methods: Hospitals in Massachusetts (n⫽24) participated in a collaborative that met quarterly, with didactic and bestpractice presentations and interactive multidisciplinary team workshops. Data collection and online feedback were attained by the use of customized tool kit and interactive Web-based management tool. Data from 1738 patients admitted with coronary artery disease (CAD) were collected by hospital staff from July 1, 2000 –June 30, 2001. The differences between baseline and 10- to 12-month follow-up measurements of use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, cholesterol measurement and treatment, smoking-cessation counseling, blood pressure control and cardiac rehabilitation referral were the outcomes of interest. Results: Significant increases occurred from baseline to 10to 12-month follow-up in smoking-cessation counseling (48% [95% confidence interval {CI}, 36.6 –58.4%] to 87% [95% CI, 73.1–100.7%]), lipid treatment (54% [95% CI, 46.6 –70.2%] to 79% [95% CI, 70.2– 88.3%]), lipid measurement (59% [95% CI, 51.5– 66.0%] to 81% [95% CI,
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particularly hazardous when used with cyclosporine or with renal failure. The incidence of myopathic reaction with statin ⫹ fibrate is relatively low (0.12%), but the combination should be used with caution and patients counseled regarding the risk and symptoms. The risk of adverse muscle effects attributable to statins ⫹ niacin is much less. Benefit-Risk Ratio: The small risk of myopathy does not outweigh the benefit of the 20 – 40% reduction in cardiovascular (CV) events in patients at risk and with CV disease. Patients should be encouraged to try lower dosing, alternative statins, possibly a hydrophilic statin, and eliminating possible drug interactions. Statin myalgias can be easily confused with flu-like syndromes. Intracellular inhibition of coenzyme Q-10 formation by statins has been demonstrated, but there is no evidence of a decrease in plasma co-Q-10, and thus far no evidence of a therapeutic benefit. Conclusions: The incidence of myopathy attributable to the statins is low, but still precludes use in a significant number of persons. Every effort should be made to ensure the statin is responsible. The combination of statins plus fibrates will be increasingly considered in the management of persons with the metabolic syndrome. Exploiting the differences between statins and fibrates might reduce the risk of drugdrug interactions. Perspective: The recent availability of ezetimibe offers other options in patients with adverse muscle reactions from statins. Ezetimibe can be used in combination with a lower statin dose, can be used alone or in combination with niacin and plant stanol. MR
familiar with the target LDL-C. The proportion of patients at LDL-C target levels at 1 year did not differ between the intervention (70.2%) and usual-care group (67.4%, p⫽0.46). At the conclusion of the trial, patient knowledge about LDL-C target level was higher for the intervention group than the usual-care group (19.6% and 6.7%, respectively, p⫽0.001), but this was not associated with improved cholesterol management. Conclusions: A nurse-based educational intervention did not result in a significant increase in the proportion of patients who reached target LDL cholesterol levels 1 year after hospitalization. Perspective: The objective was to empower the patient to make changes by providing confidence and skills to enhance the patient–physician partnership. So much for learning theory applied in clinical practice. The lack of improvement in knowledge of the target (only 19.6% at 1 year) despite five 7-minute phone calls from a nurse over the year and the materials regarding lipids, medication, nutrition sent to the patients must have been a shock to the investigators. Nearly half the subjects had a college or professional-level education. In an accompanying editorial, Eva Kline-Rogers and Kim Eagle observe, “It takes more than patient education to reach low-density lipoprotein goals.” They stress that it requires a partnership among educators, physician, and patient to make an impact, and the dissociation of the educator and physician can lead to failure. In fact, it is much better if they be one and the same or at least from the same office practice. It is well known that nurse-based lipid management is just as effective as that provided by a preventive cardiologist. So it was not the message that failed, but the method and setting of the education. MR
Clinical Trial of an Educational Intervention to Achieve Recommended Cholesterol Levels in Patients With Coronary Artery Disease
The Effect of Tai Chi on Health Outcomes in Patients With Chronic Conditions
Lichtman JH, Amatruda J, Yaari S, et al. Am Heart J 2004;147: 522– 8.
Wang C, Collet JP, Lau J. Arch Intern Med 2004;164:493–501.
Study Question: Does a nurse-based educational intervention regarding the importance of LDL cholesterol (LDL-C) and encouragement of compliance in partnership with the physician increase adherence with the NCEP target of ⱕ100 mg/dL. Methods: Patients (30 – 80 years) hospitalized with CHD were randomized either to a nurse-based educational intervention (375 patients) or usual care (381 patients) for a 12-month period after hospitalization. The primary outcome was the proportion of patients at the LDL-C target 1 year after hospitalization. The secondary outcome was the proportion of patients with accurate knowledge regarding the LDL-C target level. Results: A total of 2657 subjects were screened. The final cohort after exclusions and refusal (198 patients) was 756 subjects (64% of eligible patients). Overall, 88.5% of participants completed the 1-year follow-up, a similar number in the intervention and usual-care group. Mean age was 64 years, and 71% were white. At baseline, about 42% of each group was at target LDL-C and 5% of each group was
Study Question: What is the evidence for an effect of Tai Chi on various chronic medical conditions? Methods: Eleven computerized English and Chinese databases were reviewed to find randomized controlled trials, nonrandomized controlled studies, and observational studies published in English or Chinese. Data were extracted for the study objective, study design, population characteristics, study setting, type of Tai Chi, duration of follow-up and results. Results: Forty-seven studies fulfilled criteria. Nine were prior to 1990, 9 were randomized controlled trials, 23 were nonrandomized controlled studies and there were 15 observational studies. About 33% addressed cardiopulmonary function, 25% balance and 15% psychological effects. Benefits were reported in balance and strength, cardiovascular and respiratory function, flexibility, immune system, symptoms of arthritis, muscular strength, and psychological effects.
ACC CURRENT JOURNAL REVIEW May 2004
12
72.0 – 89.5%]) and cardiac rehabilitation referral (34% [95% CI, 25.9 –39.7%] to 73% [95% CI, 63.2– 82.9%]). An improving trend was also seen in blood pressure control (60% [95% CI, 55.3– 65.6%] to 68% [95% CI, 60.2–76.1%]). High baseline use was sustained for use of aspirin, beta-blockers, and ACE inhibitors. Conclusions: A collaborative quality improvement initiative using interactive training of hospital teams with physician champions, and the use of an interactive Web-based patient management tool improved adherence to prevention guidelines in hospitalized patients with CAD. Perspective: The Guideline Applied in Practice (GAP) and the Get With The Guidelines (GWTG) quality improvement initiatives demonstrate that implementation of system changes is successful in improving the quality of care of patients with CAD that ultimately results in improved outcomes of these patients. RM
Current Overview of Statin Induced Myopathy Rosenson RS. Am J Med 2004;116:408 –16. Purpose: To summarize the current knowledge and clinical implications regarding statin-induced myopathy and review the ACC/AHA/NHLBI task force recommendations. Definitions and Prevalence: Myalgia, defined as muscle ache or weakness without increase in creatine kinase levels (CK), is the most frequently occurring adverse reaction to statin therapy. It is reversible on drug withdrawl, and symptoms resolve in 2–3 weeks. Myositis is defined as muscle symptoms with increased CK levels. Rhabdomyolysis (rhabdo) is defined as muscle symptoms associated with CK levels ⬎10 times upper limit of normal, and can be life threatening. Dose-dependent myotoxic effects from myalgia to rhabdo ranges from 1–7%. Myopathy, a disease of muscle that can occur in the absence of CK elevation, is rare, with an incidence of 1.2/10,000 person-years, which is similar to the general population. Rhabdomyolysis occurred in 0.05% of patients receiving simvastatin and 0.03% on placebo in the Heart Protection Study. Cerivastatin (most on 0.8 mg dose) caused 31 fatal cases of rhabdo in the U.S., and 12 were on concomitant gemfibrozil. Cerivastatin had a 16- to 80-fold higher rate of rhabdo than did other statins (3.16/ million with ceriva, 0.19 lova, 0.12 simva, 0.04 atorva, 0.04 prava and 0 with fluva). Lipophilicity is believed to increase the possibility of adverse effects on muscle, but prava and rosuva, which are both hydrophilic, do not seem to have fewer muscle issues. The risk of myopathy increases with age, in women, in renal failure, with concomitant use of drugs that inhibit or use the CYP3A4 pathway (e.g., cyclosporine, erythromycin, anti-fungals), grapefruit juice, and hypothyroidism. Concomitant use of gemfibrozil inhibits glucuronidation, a common metabolic pathway for hydroxyl acid forms of statins, and marked increases statin concentration and risk of myopathies. In contrast, fenofibrate does not have the same effects and may be safer with the statins. The combination of statin ⫹ fibrate would be
Get With the Guidelines for Cardiovascular Secondary Prevention. Pilot Results LaBresh KA, Ellrodt AG, Gliklich R, Liljestrand J, Peto R. Arch Intern Med 2004;164:203–9. Study Question: Does the use of Web-based technology and a collaborative model improve hospital adherence to secondary prevention guidelines? Methods: Hospitals in Massachusetts (n⫽24) participated in a collaborative that met quarterly, with didactic and bestpractice presentations and interactive multidisciplinary team workshops. Data collection and online feedback were attained by the use of customized tool kit and interactive Web-based management tool. Data from 1738 patients admitted with coronary artery disease (CAD) were collected by hospital staff from July 1, 2000 –June 30, 2001. The differences between baseline and 10- to 12-month follow-up measurements of use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, cholesterol measurement and treatment, smoking-cessation counseling, blood pressure control and cardiac rehabilitation referral were the outcomes of interest. Results: Significant increases occurred from baseline to 10to 12-month follow-up in smoking-cessation counseling (48% [95% confidence interval {CI}, 36.6 –58.4%] to 87% [95% CI, 73.1–100.7%]), lipid treatment (54% [95% CI, 46.6 –70.2%] to 79% [95% CI, 70.2– 88.3%]), lipid measurement (59% [95% CI, 51.5– 66.0%] to 81% [95% CI,
ACC CURRENT JOURNAL REVIEW May 2004
11
particularly hazardous when used with cyclosporine or with renal failure. The incidence of myopathic reaction with statin ⫹ fibrate is relatively low (0.12%), but the combination should be used with caution and patients counseled regarding the risk and symptoms. The risk of adverse muscle effects attributable to statins ⫹ niacin is much less. Benefit-Risk Ratio: The small risk of myopathy does not outweigh the benefit of the 20 – 40% reduction in cardiovascular (CV) events in patients at risk and with CV disease. Patients should be encouraged to try lower dosing, alternative statins, possibly a hydrophilic statin, and eliminating possible drug interactions. Statin myalgias can be easily confused with flu-like syndromes. Intracellular inhibition of coenzyme Q-10 formation by statins has been demonstrated, but there is no evidence of a decrease in plasma co-Q-10, and thus far no evidence of a therapeutic benefit. Conclusions: The incidence of myopathy attributable to the statins is low, but still precludes use in a significant number of persons. Every effort should be made to ensure the statin is responsible. The combination of statins plus fibrates will be increasingly considered in the management of persons with the metabolic syndrome. Exploiting the differences between statins and fibrates might reduce the risk of drugdrug interactions. Perspective: The recent availability of ezetimibe offers other options in patients with adverse muscle reactions from statins. Ezetimibe can be used in combination with a lower statin dose, can be used alone or in combination with niacin and plant stanol. MR
familiar with the target LDL-C. The proportion of patients at LDL-C target levels at 1 year did not differ between the intervention (70.2%) and usual-care group (67.4%, p⫽0.46). At the conclusion of the trial, patient knowledge about LDL-C target level was higher for the intervention group than the usual-care group (19.6% and 6.7%, respectively, p⫽0.001), but this was not associated with improved cholesterol management. Conclusions: A nurse-based educational intervention did not result in a significant increase in the proportion of patients who reached target LDL cholesterol levels 1 year after hospitalization. Perspective: The objective was to empower the patient to make changes by providing confidence and skills to enhance the patient–physician partnership. So much for learning theory applied in clinical practice. The lack of improvement in knowledge of the target (only 19.6% at 1 year) despite five 7-minute phone calls from a nurse over the year and the materials regarding lipids, medication, nutrition sent to the patients must have been a shock to the investigators. Nearly half the subjects had a college or professional-level education. In an accompanying editorial, Eva Kline-Rogers and Kim Eagle observe, “It takes more than patient education to reach low-density lipoprotein goals.” They stress that it requires a partnership among educators, physician, and patient to make an impact, and the dissociation of the educator and physician can lead to failure. In fact, it is much better if they be one and the same or at least from the same office practice. It is well known that nurse-based lipid management is just as effective as that provided by a preventive cardiologist. So it was not the message that failed, but the method and setting of the education. MR
Clinical Trial of an Educational Intervention to Achieve Recommended Cholesterol Levels in Patients With Coronary Artery Disease
The Effect of Tai Chi on Health Outcomes in Patients With Chronic Conditions
Lichtman JH, Amatruda J, Yaari S, et al. Am Heart J 2004;147: 522– 8.
Wang C, Collet JP, Lau J. Arch Intern Med 2004;164:493–501.
Study Question: Does a nurse-based educational intervention regarding the importance of LDL cholesterol (LDL-C) and encouragement of compliance in partnership with the physician increase adherence with the NCEP target of ⱕ100 mg/dL. Methods: Patients (30 – 80 years) hospitalized with CHD were randomized either to a nurse-based educational intervention (375 patients) or usual care (381 patients) for a 12-month period after hospitalization. The primary outcome was the proportion of patients at the LDL-C target 1 year after hospitalization. The secondary outcome was the proportion of patients with accurate knowledge regarding the LDL-C target level. Results: A total of 2657 subjects were screened. The final cohort after exclusions and refusal (198 patients) was 756 subjects (64% of eligible patients). Overall, 88.5% of participants completed the 1-year follow-up, a similar number in the intervention and usual-care group. Mean age was 64 years, and 71% were white. At baseline, about 42% of each group was at target LDL-C and 5% of each group was
Study Question: What is the evidence for an effect of Tai Chi on various chronic medical conditions? Methods: Eleven computerized English and Chinese databases were reviewed to find randomized controlled trials, nonrandomized controlled studies, and observational studies published in English or Chinese. Data were extracted for the study objective, study design, population characteristics, study setting, type of Tai Chi, duration of follow-up and results. Results: Forty-seven studies fulfilled criteria. Nine were prior to 1990, 9 were randomized controlled trials, 23 were nonrandomized controlled studies and there were 15 observational studies. About 33% addressed cardiopulmonary function, 25% balance and 15% psychological effects. Benefits were reported in balance and strength, cardiovascular and respiratory function, flexibility, immune system, symptoms of arthritis, muscular strength, and psychological effects.
ACC CURRENT JOURNAL REVIEW May 2004
12